Every multicellular organism contains stem cells that have the ability to differentiate into any other cell in the body. Because stem cells are essentially precursors of many other cell types, there has been much research interest in elucidating their cellular mechanisms. Imagine the promise of being able to culture replacement tissues or even whole organs from stem cells. Additionally, the potential for using stem cells to repair damaged tissues may be applicable to a wide range of disease conditions.
Mammalian stem cells typically originate from three sources. Embryonic stem cells are obtained from early embryos, particularly the blastocyst stage of embryonic development. Adult stem cells are those which are found in adult tissues, which generally contain at least a small complement of these primordial cells that can further develop into the specialized cells of the particular tissue and thereby provide a repair function. Lastly, cord blood stem cells are obtained from umbilical cord blood obtained around the time of birth.
Embryonic stem cells, in particular, are at the center of a politico-religious controversy focused on the need for destroying a fertile human embryo when harvesting the stem cells. This debate has caused the federal government, at least to date, to deny research funding for projects involving embryonic stem cells.
A stem cell is characterized by the ability to renew itself, that is, it maintains its undifferentiated state while undergoing many cycles of cell division; it proliferates, yet it remains a progenitor cell. Secondly, to be considered a stem cell, it must retain the ability to morph into any other cell type. The term “stem cell” is sometimes also applied to progenitor cells that have the ability to form only a specific type of mature cell.
Stem cells are described by the scope of their potency, that is, by the range of mature cells which the stem cell can differentiate into. Totipotent stem cells possess the broadest developmental ability and can form any other downstream cells. Totipotent stem cells are formed very early in the embryonic cycle, for example, from a fertilized egg and its first few divisions. Pluripotent stem cells develop from totipotent cells and have the ability to form cells of any of the three germ layers in the body: ectoderm, endoderm and mesoderm.
In vitro culture of stem cells may cause a change in the biochemistry of the cells and may result in stem cells which do not behave as they might be expected to in vivo. Accordingly, there is disagreement in the scientific community as to whether some presently maintained cell lines are truly to be considered stem cells.
The earliest type of stem cell, embryonic stem cells (ESCs), originate in the blastocyst stage of an embryo, which in the human would be about four or five days old and contain up to about 150 cells. ESCs can differentiate into any cell type in the adult body, of which there are over two hundred types. Obviously, such differentiation would require the proper nutrition and growth conditions, as well as the correct stimuli for development.
To date, just about all research has been based on mouse embryonic stem cells (mESCs) and on human embryonic stem cells (hESCs). These two cells types have the required characteristics of stem cells but demand quite different culture conditions and environment, without which they will quickly differentiate, losing their stem cell potential. Human ESCs are further defined by the presence of certain cell markers, including transcription factors and cell surface proteins. These include Oct-4, NANOG, and Sox2, all transcription factors which help suppress genes that, if active, would lead to differentiation. Also, SSEA3 and SSEA4 cell surface glycolipids as well as Tra-1-60 and Tra-1-81 surface antigens. Other markers which may help identify a stem cell are being studied as well.
An “adult stem cell” is one which is found in the fully developed organism but which yet retains its ability to divide to form others like itself and also retains the ability to differentiate into more specialized cells. These cells are also known as somatic stem cells and are found not only in adults but also in children. Somatic stem cells are typically restricted in their differential capacity so that they are able to form a limited range of more specialized cells. Accordingly, they are often named by their tissue of origin, for example, mesenchymal stem cells, endothelial stem cells, and others.
Much research has been devoted to environmental factors that influence the differentiation of stem cells or even the regression of differentiated cells back to undifferentiated stem cells. In fact, there have been very recently two reports describing the generation of stem cells from fully differentiated skin cells. The potential is there for regressing fully differentiated cells into stem cells which can then be differentiated into yet other types of specialized cells. This is of great interest, as it would completely render moot the argument over destruction of a human embryo in order to obtain hESCs.
When stem cells divide, they may form two stem cell daughter cells (symmetric division), or may form one stem cell and one daughter cell having less potential (asymmetric division). How this process is determined is unknown at this time. One school of thought holds that the specific segregation of cell membrane proteins may determine asymmetric division. In our view, this uneven segregation of cell membrane proteins is more likely a symptom of asymmetric division, rather than a cause of it. Another school of thought holds that environmental factors influence stem cells to remain undifferentiated. If these environmental factors change in some way, then the stem cells will differentiate.